On May 17, 2016, the U. S. Food and Drug Administration granted accelerated approval to nivolumab (Opdivo, marketed by Bristol-Myers Squibb) for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (Adcetris).

The approval was based on two single-arm, multicenter trials of nivolumab in adults with relapsed or refractory cHL. The trials enrolled patients regardless of PD-L1 expression status on Reed-Sternberg cells. The primary efficacy endpoint was objective response rate (ORR) as determined by an independent radiographic review committee. Additional outcome measures included duration of response (DOR).

Safety was evaluated in 263 patients with relapsed or refractory cHL. Ninety-eight per cent of patients had received autologous HSCT. Patients received a median of 10 doses of nivolumab (range: 1, 48) at the approved dose-schedule. The most common (reported in at least 20%) adverse reactions of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea. Additional common adverse reactions (reported in at least 10%) included rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis.

Other immune-mediated adverse reactions, occurring in 1% to 5% of patients, included rash, pneumonitis, hepatitis, hyperthyroidism, and colitis. Serious adverse reactions were reported in 21% of patients. The most common SAEs, reported in 1% to 3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

A new “Warning and Precaution” was issued for complications of allogeneic HSCT after nivolumab. Transplant-related deaths have occurred, and health care professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions. FDA has required the manufacturer to further study the safety of allogeneic HSCT after nivolumab.

The recommended dose-schedule of nivolumab is 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

Continued approval for the cHL indication may be contingent upon verification of clinical benefit through a randomized phase 3 trial.

This application was approved before the Prescription Drug User Fee Act (PDUFA) goal date of September 1, 2016. Nivolumab was granted Breakthrough Therapy Designation for the treatment of relapsed or refractory cHL after failure of autologous HSCT and brentuximab vedotin. Nivolumab also has Orphan Drug status for the treatment of HL. This application was granted Priority Review and was approved under FDA’s Accelerated Approval Program. A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/ guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).